High Maintenance Dosage of Clopidogrel is Associated with a Reduced Risk of Stent Thrombosis in Clopidogrel-Resistant Patients

Background

Stent thrombosis remains an important complication after stent implantation, despite the use of dual antiplatelet therapy with aspirin (acetylsalicylic acid) and clopidogrel. Several studies have shown an increased risk of thrombotic events in patients with resistance to clopidogrel. Some recent studies have suggested that a higher clopidogrel maintenance dosage could enhance ex vivo platelet inhibition and thereby overcome resistance to clopidogrel.

Objectives

To investigate whether a higher clopidogrel maintenance dosage is associated with a reduced risk of stent thrombosis after percutaneous coronary intervention (PCI) in clopidogrel-resistant patients and to evaluate the frequency of hemorrhagic accidents that could be associated with a high clopidogrel maintenance dosage.

Methods

An observational study was performed in 52 consecutive clopidogrel-resistant patients (resistance defined according to adenosine diphosphate-induced platelet aggregation assessment) who underwent a PCI with stenting at a tertiary referral center (Toulouse University Hospital, France). All patients received a clopidogrel loading dose of 300 mg, then 32 patients received a clopidogrel maintenance dosage of 75 mg/day (patients admitted between 2004 and 2005) and 20 patients received 150 mg/day (patients admitted in 2006). We compared the occurrence of definite stent thrombosis and hemorrhagic accidents between these two groups, using a regression model.

Results

Among the patients treated with clopidogrel 75 mg/day, 26 (81.3%) had definite stent thrombosis versus seven (35.0%) treated with 150 mg/day (adjusted relative risk [RR] 2.46; 95% CI 1.63, 2.76; p = 0.002). The risk of major adverse cardiac events (MACE) was also significantly lower in patients treated with 150 mg/day (adjusted RR 2.63; 95% CI 1.82, 2.82; p = 0.001). There was no significant difference between the two groups regarding hemorrhagic accidents.

Conclusion

Our data suggest that a high maintenance dosage of clopidogrel (150 mg/day) is associated with a reduced risk of definite stent thrombosis and MACE compared with a maintenance dosage of 75 mg/day. The frequency of hemorrhagic accidents was similar between the two groups, underlining a positive benefit-risk ratio of this strategy in clopidogrel-resistant patients. These findings deserve confirmation in a prospective, well conducted study.     

Rationale for a model of human systems integration: the need of a theoretical framework

Human systems integration (HSI) involves augmented human design with the objectives of augmenting human capabilities and improving human performance using behavioral technologies. The fundamental matter of human systems integration and augmented human design is the organization and the nature of interactions that couple physiological systems, humans- and engineered systems, artifacts. By this definition, augmented human consists of interactive artefacts linked to physiological systems. This paper focuses on the rationale of a HSI model based on specific experiments (comparison of dynamical sensorimotor integration and motor performances in real and virtual environments) that confirm the hypothesis of functional interaction in the framework of Chauvet's mathematical theory of integrative physiology (MTIP). Epistemological constraints for HSI and the role of MTIP are briefly discussed in this context.     

Ontogeny of the somatostatin variant [Pro2,Met13]somatostatin-14 in the brain, pituitary, and sensory organs of the frog Rana esculenta

Two forms of somatostatin are expressed in the frog brain, i.e., somatostatin-14 (SS1) and the [Pro(2), Met(13)]somatostatin-14 variant (SS2). We have previously described the ontogeny of SS1-immunoreactive cells in the brain of Rana esculenta. In the present study, we have investigated the distribution of prepro-SS2 (PSS2)-expressing neurons in the brain of the same species during development by using antibodies directed against the N-flanking region of SS2 (PSS2(54-66)). Immunoreactive perikarya first appeared in the ventral hypothalamus at stages IV-VII. Subsequently, positive neurons were seen in the nucleus of the diagonal band of Broca, the anterior preoptic area, the posterior tuberculum (stages VIII-XII), as well as the dorsal (stages XIII-XV) and medial (stages XIX-XX) periventricular preoptic nucleus. At metamorphic climax and in newly metamorphosed frogs, positive perikarya were found in the striatum and in the interpeduncular nucleus. PSS2(54-66)-immunoreactive fibers were already widely distributed during the first stages of development, indicating that SS2 may act as a neuromodulator and/or neurotransmitter during ontogeny. The presence of PSS2(54-66)-positive nerve fibers in olfactory structures suggests that, in tadpoles, SS2 may be involved in the processing of olfactory information. The occurrence of PSS2(54-66)-like immunoreactivity in taste buds, and in the olfactory and vomeronasal organs indicates that SS2 may mediate the unconditioned and reinforcing properties of natural chemicals. Finally, the intenseexpression of PSS2(54-66)-like immunoreactivity in melanotrope cells of the pituitary suggests that SS2 may diffuse toward the pars distalis to regulate the activity of adenohypophysial cells during tadpole development.     

Culture of C. burnetii from the dental pulp of experimentally infected guinea pigs

An experimental model of Q fever in Guinea pigs was studied. Coxiella burnetii was cultured from the dental pulp of infected animals following bacteremia.     

Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [11C]methionine PET

Background

Dysembryoplastic neuroepithelial tumors (DNTs) represent a prevalent cause of epileptogenic brain tumors, the natural evolution of which is much more benign than that of most gliomas. Previous studies have suggested that [¹¹C]methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumors, and hence optimize the management of patients. Here, we reassessed the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms in a larger population.

Methods

We conducted a retrospective study of 77 patients with focal epilepsy related to a nonrapidly progressing brain tumor on MRI who underwent MET-PET, including 52 with a definite histopathology. MET-PET data were assessed by a structured visual analysis that distinguished normal, moderately abnormal, and markedly abnormal tumor methionine uptake and by semiquantitative ratio measurements.

Results

Pathology showed 21 DNTs (40%), 10 gangliogliomas (19%), 19 low-grade gliomas (37%), and 2 high-grade gliomas (4%). MET-PET visual findings significantly differed among the various tumor types (P < .001), as confirmed by semiquantitative analyses (P < .001 for all calculated ratios), regardless of gadolinium enhancement on MRI. All gliomas and gangliogliomas were associated with moderately or markedly increased tumor methionine uptake, whereas 9/21 DNTs had normal methionine uptake. Receiver operating characteristics analysis of the semiquantitative ratios showed an optimal cutoff threshold that distinguished DNTs from other tumor types with 90% specificity and 89% sensitivity.

Conclusions

Normal MET-PET findings in patients with an epileptogenic nonrapidly progressing brain tumor are highly suggestive of DNT, whereas a markedly increased tumor methionine uptake makes this diagnosis unlikely.     

Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report

A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction.     

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria

Background

Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry.

Methods

Thirty-five qualitative criteria were defined (scores 0–3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student.

Results

The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0–2 for SNR <2, 2–5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0–2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83.

Conclusions

The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.     

Predictors of pneumocystosis or tuberculosis in HIV-infected Asian patients with AFB smear-negative sputum pneumonia

OBJECTIVES: To identify predictors of Pneumocystis jiroveci pneumonia (PCP) or pulmonary tuberculosis (TB) in acid-fast bacillus smear-negative HIV-infected patients and to develop clinical prediction rules. DESIGN: A cohort study conducted in consecutive hospitalized Asian patients. METHODS: Multivariate analyses were performed on the Cambodian sample to determine clinical, radiological, and biological predictors of PCP or TB at hospital admission. The Vietnamese sample was kept for independent validation. RESULTS: In Cambodia, the gold standard technique for TB and PCP were fulfilled in 172 (27 cases) and 160 (84 cases) patients, respectively. For TB, independent predictors included the following: headache [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.04 to 8.6], localized radiological opacity (OR 5.8; 95% CI 1.9-17.9), and mediastinal adenopathy (OR 10.1; 95% CI 3.5 to 29.0); and for PCP: resting oxygen saturation <90% (OR 3.3; 95% CI 1.3 to 8.5 for resting arterial oxygen saturation >or=80%; and OR 9.1; 95% CI 1.8 to 44.5 for resting arterial oxygen saturation <80%), trimethoprim-sulphamethoxazole prophylaxis (OR 0.1; 95% CI 0.04 to 0.6), and diffuse radiological shadowing (OR 7.0; 95% CI 2.7 to 18.6). PCP risk predicted by a score based on these 3 factors ranged from 3% to 92% (Cambodia). When tested on Vietnamese patients (n = 69, 38 with PCP), the score maintained correct predictive ability (c-index = 0.72) but with poor calibration. CONCLUSIONS: The PCP score could provide a useful clinical tool to identify PCP among acid-fast bacillus smear-negative pneumonia and start specific therapy.     

Genome-wide, high-resolution DNA methylation profiling using bisulfite-mediated cytosine conversion

Methylation of cytosines ((m)C) is essential for epigenetic gene regulation in plants and mammals. Aberrant (m)C patterns are associated with heritable developmental abnormalities in plants and with cancer in mammals. We have developed a genome-wide DNA methylation profiling technology employing a novel amplification step for DNA subjected to bisulfite-mediated cytosine conversion. The methylation patterns detected are not only consistent with previous results obtained with (m)C immunoprecipitation (mCIP) techniques, but also demonstrated improved resolution and sensitivity. The technology, named BiMP (for Bisulfite Methylation Profiling), is more cost-effective than mCIP and requires as little as 100 ng of Arabidopsis DNA.